J-monocarboxylicacids-j-thiono



where each of R1, 2, R3, R4 and R5 is "or-a hydrocarbon group and R is a divalent Patented July 4, 1950 UNITED STATES 1 ;\1 ".1a:1- 1.'1" OFFICE S-MONOCARBOXYLIC ACID S -2-THION O- v THIAZINES AND THEIR PRODUCTION Roger A. Mathcs and Floyd D. Stewart, Akron,

Ohio, assignors to TheB, 'F. Goodrich Company, New York, N. Y.', a corporation of New York I N6 Drawing. Application September 24,1949,

Serial No.117,737 1 1 invention relates I to 3-substituted 2- thiono-thiazines and pertains more specifically to Z-thiono-thiazines having the residue of a monocarboxylic acid or its ester attached by a carbon atomapart from its functional group to,

the nitrogen atom in the 3 position of the thiazine ring. The invention also includes the i method of making these 3-substituted 2-thionothiazines. Y V The 3-substituted Z-thiono-thiazines of this 10 invention possess the following general formula:

hydrogen hydrocarbon radical. These compounds will sometimes be referred to hereinafter as 2- thiono-thiazine-3-monocarboxylic acids and esters. They are useful as intermediates in the synthesis of organic compounds, in the compounding of natural and synthetic rubbers and resins, and as insecticides-fungicides and regulators for plant growth.

These 2-thiono-thiazine 3 monocarboxylic acids and ester are prepared byreacting an alpha, beta-olefinically-unsaturated aldehyde or ketone, that is, an aldehyde or ketone containing the structure 2 with a dithiocarbamic acid derived from a primary-amino-substitutedmonocarboxylic acid or i a ubstitutea-atmono-tmazme 5 Claims. (omen-#243) ketone or aldehyde.

where R1, R2, R3, R4, R5 and R have the significance as indicated above.

Thedithiocarbamic acid employed as a reactant is preferably generated in situ, because of the general instability of free dithiocarbamic acids. This is conveniently accomplished by adding a salt of thedithiocarbamic acid to an acid solution or suspension of the unsaturated The dithiocarbamic acid saltsso used are, in turn, first prepared preferably by reacting the amino acid or ester with carbon disulfide, generally in an alkaline medium.

ester thereof. This reaction proceeds as followsz m namaldehyde, I alpha-ethyl .3

The following equation illustrate this reaction when carried out in the presence of sodium hydroxide where the sodium salt of the dithiocarbamic acid is formed:

' Again, R and R5 have the significance indicated above;

' -Am'ong the unsaturated aldehydes containing the group which fw111 react'with the dithiocarbamic acids of amino'acids and'esters of amino acids to give the 3-substitute'd Z-thiono-thiazines of this invention, are acrolein, methacrolein, tiglic aldehyde, 2-ethyl-2-hexenal, crotonaldehyde, cinacrolein, alphamethyl-beta-ethyl acrolein, alpha-propyl acrousein this invention are those which possess the formula set forth above wherein each of R1, R2

and Rs ishydrogen or a hydrocarlpmn radical con- 3-amino-2-naphtlioic acid,

case of ketones. I

The other reactant employed in the=process of this invention isthe dithiocarbamic.acid of any amino acid or hydrocarbon ester thereof having the formula as hereinbefore set forth. For eX-f ainple, this includes the dithiocarbarnic acids of alanine, amino sec-butyl acetic acid (isoleucine) i-amino-butyric acid,

thiazines of this invention. In Example I all parts are by weight.

EXAMPLE I To an aqueous solution containing 40 parts of sodium hydroxide dissolved in "200,p,'arts of water 121241111110 .buty'ric :Jacid,

2-a1nino butyric acid, Z-aminoeLI-EdiethyI b'utyric acid, l-amino 2,2-dimethyl butyric -acidg3aminoe- 2,3 diphenyl butyric acid, l-amino 1 ethyl butyric acid, l-amino l-methylbutyriceacid (isovaline), 'l-amino 1 phenyl butyric zaacid,

3 (o aminophenyl) butyric acid, 1 amino caproic acid, 4-amino caproic acid, 5-amino 2;4'-

dimethyl caproic acid, 5-amino caproic acid,

2 amino 2 methyl caproic acid,- 5 amino- 3-methyl caproic a cim l-amino caprylic -acid, 5-amino-3AA-trimethyl capr ylic acid, l' amino noethyl) benzoic acid, p-(3-aminopropyl) benzoic 3-amino-1-naphthoic acidg G-amind-l naiahthoic acid, B-amino-l-naphthoic acid, 2-amino-5,6,'7,8- tetrahydronaphthoic acid, aearnino; 5,6, 7,8-tet rahydronaphthoic acid,l-amino-Z-naphthoic acid,

2 naphthoic acid, l-amino-G-methyl-Z-naphh i cid. 1; amino. '7.---. methyl naphthoic acid, '1 amino 5,6,7,8-tetrahydronaphthoic:acid

and 3 amino '9, 51537,SrtetrahydrQnaphthOic: acid.

; and isobutylesters; the; cycloallg-yl esters such as the cyclohexyl esterS; lihe aryl esterssuch as the phenyl and naphthyl esters; and theiaralkyl v esters such as the benzyl and; phenethyl esters.

The following--;are specific examples of dithio-' carbamic sacid; .a few; of" the easily; obtainable and preferredaminoacids; set forthabovendithio-g carbamic acid ofglycine,

ueo- -N-(imo 0 OH dithiocarbamicacid of beta alanine, HS('T N-,CH:OHzC.O-OH

' dithiocar-bamic acid oi 'alphaalanine,

and dithiocarbamic acid of p-iaminogbenz'oicacid,

The preparationof the sodium dithiocarbamate salt of glycine-set forth -in Example I illustrates the method of; obtainingthe-redotantfregdiied for the preparatiorr'of-the 3-substituted 2 thiono-* acetic acid). This mixture was stirred and cooled to 20 C. Then 38.0 parts of carbon disulfide were such amino acids as glycine, alphaealanme,"Jbeta- 1Q ,afgded to the ml'xt'ure he reactlon mlxture was maintained at 20 C. and was stirred for about 2 hours at which time the reaction was complete as' e idenced"b bhe"'disappearance of the carbon -disuliide layer. 1111 this manner a solution containing 82 parts of a Na S T(IJ-N-CHIO 0 0 H was prepared.

The following specifically detailed examples illustrate t e es at on f he. 3.s h .t tu

h 'o o h azi fi ;i Qfth in ention, Again. a --pa ar by wei ht- The aqueous solution of the sodium 'dithio- "carbam'ate salt of glycine 1prepared= in-Example I acid, .m-aminobenz'oic --acid; m- (p-aminophenyl) '30 Y -be'nzoic a'cid, -4-ainino 2 phenyl benzoic acid, 0- (p-aminophenyl) benzoic acid, anthranilic acid, H 3,5-di1nethyl 1a'r'ithrani1idac'id, 3,6=-'dimethy1 anthrani-lic; acid Bfpheirryl anthran ilic acid, 3-ami- 1-amino-3 -methyl 4o;

*is in agreement with thecalculated che'mical com- 1 tha ol; were esins/ red.

fied as 4536- 11 e le-zeth npv'afi;dihydro-th -azineea-acetioracid ay sthe or n a.

was iadded with vigorous stirring 'to a; solution containing '49 parts "of-'-mesityloxide dissolved in 198 parts of hydrochloric acid containingli'l parts ofhydrogeni chloride. This mixturewas stirred" and heated to-"-" Cr and maintained at that temperature for about one hour. A solid material formed during-,thareaction. This solid material was recovered by filtration after the mixture resulting iromathereadtion was cooled to room temperature. In manner 28 parts of a solid product, which had a melting point of 157 C. to 159 C. aften recrystallization from h nr duetrwasiden The chem-icalfi analysis; ofthes-v product prepared positionas indicated below.

Percentage composition Calculated By Analysis o -H N s. 1' M. w 231 M w 232 EXAMPLE III An aqueous-solution:containing 82aipartszof- NaS-C|N-OH:COOH

reaction. After cooling the solid reaction prod-41.

uct was recovered by filtration. In this mariner-- a yield of 110 parts of the solid reaction product, which was identified as 6-phenyl-2-thiono-3,6- di hydro-thiazine-3-acetic acid, were recovered.

but the reaction rate is slow. The reaction can also be carried out at temperatures above 60 C but excessive heating will result in the decompositionvof the dithiocarbamic acid. The useful This material after extraction with ethanol and recrystallizing from chloroform hada melting point of 178 C. to 179 C. A chemical analysis 1 of this product gave the percentage composition as tabulated below which is in close agreement with the calculated composition for the above--- named compound.

Percentage composition Calculated By Analysis range of temperature for the reaction is from about 20 C;'to about 100 C. with the preferred temperature range being from about C to about C. I v 1 Any of the unsaturated aldehydes vand ketones hereinbefore named can be substituted for m'esityl oxide of Example II or cinnamaldehyde of Example III to prepare other 2-thiono-thiazine-3- monocarboxylic acids and esters of this invention. Also the dithiocarbamic acid derivatives of the hereinbefore named amino acids and esters can be substituted for the dithiocarbamic acid derivative of glycine (amino acetic acid) employed in Examples II and III to prepare other z-thiono-thiazine-3-monocarboxylic acids and esters of this invention.

The following examples in tabular form illustrate the use of other aldehydes, ketones, dithiocarbamic acid derivatives of amino acids and esters and the resulting 3-substituted-2-thionothiazines of this invention.

EXAIMPLES IV to XII Amino Acid Whose Dithio- Unsaturated g or Kewne carbamic Acid Derivative is Product Used IV v fl) '-H:|NCH1CH|COOH /S\ OHy=CH- CH beta alanine H10 I =8 Acrolein H rr-omcmcoon 2-thiono-3,6-dihydrothiazine-3-propionic acid v 0 0 mm s H g I! 'CsH1(!=C -H H N C-OH CzH -C $=S El) ,3, H- NOC '-OH p-amino benzoic acid A 2-ethylhexcnal i 6 ethyl-6-n-propyl-2-thiono-3,6-dil1ydrothiazine-3-p-benzoic acid VI v O S I! II E CHQ=C--C-H H:N C-OCdEh H: 1 =3 1') I 1H1 I CaHr-( I N-OC-O 04H) Butesin alpha-propylacrolein g 5-n-prcpyI-2-thiono-3,6-dihydro-thiazine- 3-p-benzoic acids-butyl ester 7 v11 0 I era. 7 s it 0 I om=on- -cH, H20 0:5 0.

- CHIOHr- OH I l, Methyl Vinyl ketona I l H N-CCOH- NH: I

- C CzHs CzHs l-amino-l-ethylbutyric acid I A 4-methyl-2-thiono-3,6-dihydro-thiazine 3-diethyl acetic acid vm o l s g --i "i ll' I CHg=C- CHgCHsCHzC-OH H20 $=S H Phony] vinyl am NH, H )N-omo memo-0H n' 3-amiuo butyrioacid c 4-phenyl- 2 thiono-3,fi-dil ydro-thiazinw l; butyric Mild cific examples which are intended merely to be iselected from the group consisting of hydrogen illustrative;.ofieour processnand the products ob- 1 and hydrocarbon radicalsland R is a divalent tained thefeby and which are not to be construed I hydrocarbon group.

as limitations thereon, We do not desiremr intend 2. 4,6,6 trimethyl-2-thiono-3,6-dihydro-thiato 1imit..ourse1ves"sole1y.thereto, for. as hitherto IZine-Beaceticacid having the formula stated the proportions of the materia1s uti1ized Hi0 s and the reaction conditions may be varied and 60 6 chemical equivalent compounds may be used, if (1/ desired, without .departing from=the spifitand-" l scope of our invention as defined in the appended H N-omooon claims. 7

We claim: A

1. A com ound having the formula l p p I I 3. s phenylel-thiono 3,4 dihydro thiazine- FS-acet'ic acid having the formula 4. A 2-thiono-thiazine-3-acetic acid having the formula Rr-l N-CHaCO OH Rf Mi wherein each of R1, R2, R3 and R4 is a member of the group consisting of hydrogen and hydrocarbon radicals with a salt of a dithiocarbamic acid of the formula 10 wherein R5 is a member of the group consisting of hydrogen groups and R is a divalent hydrocarbon radical, in an acidic aqueous medium at a temperature of 20 to C. and recovering from the reaction medium a compound of the formula R1\ /S\ Rr-C C=B N-Rl-(fi-O-Jt wherein R1, R2, Ra, R4, R5 and R have the same significance as indicated above.

ROGER A. MATHES. FLOYD D. STEWART.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,086,186 Messer July 6, 1937 2,466,396 Dickey Apr. 5, 1949 Certificate of Correction Patent N 0. 2,514,004 July 4, 1950' ROGER A. MATHES ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows:

Column 3, lines 57 to 59, for that portion of the formula reading c c I; read it column 4, lines 66 to 68, for

N N E read t columns 5 and 6, Example VII, first column thereof, in the formula, for

'L CH! read L)CH| column 10, line 2, after the word hydrogen insert and hydrocarboh;

and that the said Letters Patent should be read as corrected above, so that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 17th day of October, A. D. 1950.

THOMAS F. MURPHY,

Assistant Commissioner of Patents. 

1. A COMPOUND HAVING THE FORMULA 